This program project will primarily use genetic modified mice. The Animal Core will provide essential genetically modified mice and control wild-type mice to support the research of all four projects. To accomplish this objective, the Animal Core will be responsible for: 1) establishing, maintaining and breeding the required numbers and ages of knock-in, knockout and transgenic mice;2) characterizing gene altered mice using molecular, biochemical, and pathological methods to ensure genotype and phenotypes;3) performing the complex genetic crosses required to obtain mice with the desired combinations of mutations; and 4) providing pups at the desired gestation stages and ages to establish primary culture cells. By coordinating and standardizing animal and cell use among projects, animals, money, and time will be saved. Providing every project with animals and cells derived in the same manner will make it possible to crosscorrelate information from the projects, which will result in synergistic use of the animals and the data generated. The Animal Core will also work closely with the Administrative Core and Core B to help the project leaders plan and/or define their studies.